Enhanced Th1 activity and development of chronic enterocolitis in mice devoid of Stat3 in macrophages and neutrophils
Open accessAbstract
We have generated mice with a cell type-specific disruption of the Stat3 gene in macrophages and neutrophils. The mutant mice are highly susceptible to endotoxin shock with increased production of inflammatory cytokines such as TNF alpha, IL-1, IFN gamma, and IL-6. Endotoxin-induced production of inflammatory cytokines is augmented because the suppressive effects of IL-10 on inflammatory cytokine production from macrophages and neutrophils are completely abolished. The mice show a polarized immune response toward the Th1 type and develop chronic enterocolitis with age. Taken together, Stat3 plays a critical role in deactivation of macrophages and neutrophils mainly exerted by IL-10.
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Macrophage- and neutrophil-specific STAT3 knockout causes high susceptibility to endotoxin shock and increased TNF-α, IL-1, and IFN-γ.
“High susceptibility to endotoxin shock, ↑ TNF-α, IL-1, and IFN-γ”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Takeda et al., 1999
STAT3-deficient macrophages, neutrophils, and dendritic cells and hematopoietic-specific STAT3-KO mice have increased production of inflammatory cytokines.
“STAT3-deficient macrophages, neutrophils, and DCs”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Takeda et al., 1999
STAT3 suppresses TLR signaling in mature phagocytes by suppressing NF-κB and MAPK through direct transcriptional repression of an E2 ubiquitin-conjugating enzyme required for TLR signaling.
“STAT3 suppresses TLR signaling in mature phagocytes”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Takeda et al., 1999
Genetic deletion of STAT3 in innate immune cells, such as myeloid cells (neutrophils and macrophages), and enterocytes results in chronic colitis.
“In contrast, genetic deletion of STAT3 in innate immune cells, such as myeloid cells (neutrophils and macrophages), and enterocytes resulted in chronic colitis (Takeda et al., 1999; Atreya et al., 2000; Yamamoto et al., 2000; Suzuki et al., 2001; Pickert et al., 2009).”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Takeda et al., 1999
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- Authors
- Takeda, K., Clausen, B. E., Kaisho, T., Tsujimura, T., Terada, N., Förster, I., & Akira, S.
- Affiliations
- Hyogo Medical University (JP)
- University of Cologne (DE)
- Corresponding author
- Akira, Shizuo
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 1999-01
- Volume
- 10
- Issue
- 1
- Pages
- 39-49
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2078730804
- Cited by
- 1,220
- References
- 2
- Citations by year
- 2026: 6 · 2025: 19 · 2024: 20 · 2023: 30 · 2022: 31 · 2021: 26 · 2020: 33 · 2019: 38 · 2018: 32 · 2017: 45 · 2016: 52 · 2015: 53 · 2014: 51 · 2013: 62 · 2012: 62
- FWCI
- 16.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- STAT3, macrophages, neutrophils, Th1 response, chronic enterocolitis, endotoxic shock, IL-10, inflammatory cytokines, macrophage polarization, TNF-α, interferon-gamma
- MeSH terms
- Animals, Cell Differentiation, Chronic Disease, Crosses, Genetic, DNA-Binding Proteins, Enterocolitis, Lipopolysaccharides, Macrophage Activation, Mice, Inbred C57BL, Mice, Inbred Strains, Neutrophils, Shock, Septic, Trans-Activators, Interleukin-10, Macrophages, Peritoneal, Mice, Knockout, Th1 Cells, Genetic Predisposition to Disease, STAT3 Transcription Factor, Mice
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